Joint Inflammation Research Articles

Dietary fiber may benefit chondrocyte activity maintenance.

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.

Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway

Objective and designTo elucidate Sirt1’s role in gouty arthritis inflammation and its potential mechanisms.MaterialConstructed murine models of gouty arthritis and conducted THP-1 cell experiments.Treatment1 mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21 h using lipopolysaccharide (LPS) plus MSU crystals.MethodsWe assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 and Nrf2/HO-1 pathways proteins.ResultsSignificant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 and enhancing Nrf2/HO-1, thus suppressing inflammation.ConclusionsSirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.

Trans-Chalcone (1-3-diphenyl-2-propen-1-one) as a Therapeutic Candidate in Joint Inflammation via Reduction of TNF-α, IL-1β, IL-6, and IL-17 in Rodents: An In Vivo Study by RT-PCR and ELISA analysis.

Autoimmune disorders include vast and distinct illnesses and are characterized by an immune system-mediated attack on the body's own tissues. Because of their ability to impact any portion of the body, their clinical symptoms are incredibly varied. The variations in symptoms are normally linked with the release and activation of vasoactive, chemotactic substances and cytokines. Cytokines perform a multitude of vital biological tasks, such as immune response control, inflammation, proliferation, and tissue repair. The reversal of inflammatory cytokines and leukocyte infiltration into the inflamed tissue by natural compounds provides an effective remedy for autoimmune diseases. Here, the oral administration of trans-chalcone (TC) for 28 days was tested with gradually increasing doses (30, 60, and 120 mg/kg) in complete Freund's adjuvant (CFA)-provoked joint tissue stiffness in rats. Paw edema, arthritic index, joint stiffness, thermal and flexion pain, C-reactive protein, and rheumatoid factor (RF) levels were determined to check the tested drug effectiveness in a chronic inflammatory model. Molecular docking studies revealed strong binding affinity with inflammatory cytokines and mediators such as TNF-α, IL-17, COX-2, and iNOS; further, they were quantified at the mRNA level by RT-PCR and ELISA analysis. Oral administration of TC significantly ameliorated paw edema, thymus and spleen indices, joint stiffness, thermal and flexion pain, C-reactive protein, RF, mobility, and stance of the treated animals. This therapeutic effectiveness was linked with a reduction in the mRNA expression of proinflammatory cytokines such as IL-1β, IL-6, and IL-17. The findings of the reported research confirmed the effectiveness of TC in ameliorating joint stiffness and flexion pain by prominently lowering the inflammatory cytokines.

Supramolecular 3 in 1: A Lubrication and Co-Delivery System for Synergistic Advanced Osteoarthritis Therapy.

The complexity, heterogeneity, and drug resistance of diseases necessitate a shift in therapeutic paradigms from monotherapy to combination therapy, which could augment treatment efficiency. Effective treatment of advanced osteoarthritis (OA) requires addressing three key factors contributing to its deterioration: chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation. Herein, we present a supramolecular nanomedicine of multifunctionality via molecular recognition and self-assembly. The employed macrocyclic carrier, zwitterion-modified cavitand (CV-2), not only accurately loads various drugs but also functions as a therapeutic agent with lubricating properties for the treatment of OA. Kartogenin (KGN), a drug for articular cartilage regeneration and protection, and flurbiprofen (FP), an anti-inflammatory agent, were coloaded onto CV-2 assembly, forming a supramolecular nanomedicine KGN&FP@CV-2. The three-in-one combination therapy of KGN&FP@CV-2 addresses the three pathological features for treating OA collectively, and thus provides long-term therapeutic benefits for OA through sustained drug release and intrinsic lubrication in vivo. The multifunctional integration of macrocyclic delivery and therapeutics provides a simple, flexible, and universal platform for the synergistic treatment of diseases involving multiple drugs.

Role of estrogen signaling in fibroblastic reticular cellsfor innate and adaptive immune responses in antigen-induced arthritis.

Women are more prone to develop rheumatoid arthritis, with peak incidence occurring around menopause. Estrogen has major effects on the immune system and is protective against arthritis. We have previously shown that treatment with estrogen inhibits inflammation and joint destruction in murine models of arthritis, although the mechanisms involved remain unclear. Fibroblastic reticular cells (FRCs) are specialized stromal cells that generate the three-dimensional structure of lymph nodes (LNs). FRCs are vital for coordinating immune responses from within LNs and are characterized by the expression of the chemokine CCL19, which attracts immune cells. The aim of this study was to determine whether the influence of estrogen on innate and adaptive immune cells in arthritis is mediated by estrogen signaling in FRCs. Conditional knockout mice lacking estrogen receptor α (ERα) in CCL19-expressing cells (Ccl19-CreERαfl/fl) were generated and tested. Ccl19-CreERαfl/fl mice and littermate controls were ovariectomized, treated with vehicle or estradiol and subjected to the 28-day-long antigen-induced arthritis model to enable analyses of differentiated T- and B-cell populations and innate cells in LNs by flow cytometry. The results reveal that while the response to estradiol treatment in numbers of FRCs per LN is significantly reduced in mice lacking ERα in FRCs, estrogen does not inhibit joint inflammation or markedly affect immune responses in this arthritis model. Thus, this study validates the Ccl19-CreERαfl/fl strain for studying estrogen signaling in FRCs within inflammatory diseases, although the chosen arthritis model is deemed unsuitable for addressing this question.

Macrophage polarization in rheumatoid arthritis: signaling pathways, metabolic reprogramming, and crosstalk with synovial fibroblasts.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Macrophages are key effector cells that play a central role in RA pathogenesis through their ability to polarize into distinct functional phenotypes. An imbalance favoring pro-inflammatory M1 macrophages over anti-inflammatory M2 macrophages disrupts immune homeostasis and exacerbates joint inflammation. Multiple signaling pathways, including Notch, JAK/STAT, NF-κb, and MAPK, regulate macrophage polarization towards the M1 phenotype in RA. Metabolic reprogramming also contributes to this process, with M1 macrophages prioritizing glycolysis while M2 macrophages utilize oxidative phosphorylation. Redressing this imbalance by modulating macrophage polarization and metabolic state represents a promising therapeutic strategy. Furthermore, complex bidirectional interactions exist between synovial macrophages and fibroblast-like synoviocytes (FLS), forming a self-perpetuating inflammatory loop. Macrophage-derived factors promote aggressive phenotypes in FLS, while FLS-secreted mediators contribute to aberrant macrophage activation. Elucidating the signaling networks governing macrophage polarization, metabolic adaptations, and crosstalk with FLS is crucial to developing targeted therapies that can restore immune homeostasis and mitigate joint pathology in RA.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.ResultsThe surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s.ConclusionIn summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.Graphical

Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

JAKinhibs in Psoriatic Disease: Analysis of the Efficacy/Safety Profile in Daily Clinical Practice.

Psoriatic disease (PsD) affects multiple clinical domains and causes a significant inflammatory burden in patients, requiring comprehensive evaluation and treatment. In recent years, new molecules such as JAK inhibitors (JAKinhibs) have been developed. These have very clear advantages: they act quickly, have a beneficial effect on pain, are well tolerated and the administration route is oral. Despite all this, there is still little scientific evidence in daily clinical practice. This observational, retrospective, single-center study was carried out in patients diagnosed with PsA in the last two years, who started treatment with Tofacitinib or Upadacitinib due to failure of a DMARD. The data of 32 patients were analyzed, and the majority of them (75%) started treatment with Tofacitinib. Most had moderate arthritis activity and mild psoriasis involvement according to activity indices. Both Tofacitinib and Upadacitinib demonstrated significant efficacy, with rapid and statistically significant improvement in joint and skin activity indices, C-reactive protein reduction, and objective measures of disease activity such as the number of painful and inflamed joints. Although there was some difference in the baseline characteristics of the cohort, treatment responses were comparable or even superior to those in the pivotal clinical trials. In addition, there was a low frequency of mild adverse events leading to treatment discontinuation and no serious adverse events. These findings emphasize the strong efficacy and tolerability of JAKinhibs in daily clinical practice, supporting their role as effective therapeutic options for patients with PsD.

Pharmaceutical Preparation of Amrita Guggulu and its Clinical Efficacy on Vatarakta

This study scrabbles about into the pharmaceutical preparation of Amrita Guggulu, a traditional Ayurvedic formulation known for its therapeutic properties. The focus of the research is on assessing the clinical efficacy of Amrita Guggulu in managing Vatarakta, a condition characterized by vitiated Vata as well as Pitta and associated with inflammatory joint disorders. The pharmaceutical preparation involves meticulous formulation techniques, ensuring the quality and potency of the final product. Standardization parameters include the selection of authentic raw materials, adherence to traditional preparation methods and quality control measures. Clinical Trial Design: The clinical trial was designed as a randomized, double-blind study to assess the efficacy of Amrita Guggulu in patients diagnosed with Vatarakta. Participants were randomly assigned to either the treatment group receiving Amrita Guggulu group A or group B. A comprehensive clinical trial was conducted to evaluate the efficacy of Amrita Guggulu in patients diagnosed with Vatarakta. Key parameters such as joint pain, inflammation in joint, tenderness, burning sensation in affected area, skin rashes and tingling sensation were selected for the study. Overall improvement was assessed using standardized tools and patient-reported outcomes. Result: Preliminary findings indicate promising results, suggesting that Amrita Guggulu may play a significant role in alleviating symptoms associated with Vatarakta. The observed effects include a reduction in joint pain, improved joint function, and decreased inflammatory markers. Conclusion: This research contributes valuable insights into the pharmaceutical preparation of Amrita Guggulu and highlights its potential as an effective intervention for Vatarakta. On the basis of this clinical trial, we can say that S. Uric acid is not the confirmatory parameter for the decision of Vatarakta (gout). Further studies and long-term observations are recommended to solidify these findings and establish Amrita Guggulu as a viable therapeutic option in managing inflammatory joint disorders.

Chinese medicine Di-long (Pheretima vulgaris) and its active fraction exhibit anti-rheumatoid arthritis effects by inhibiting CXCL10/CXCR3 chemotaxis in synovium

Ethnopharmacological relevanceDi-Long (Pheretima vulgaris) is a classic animal sourced traditional Chinese medicine. It has been used for the treatment of joint inflammation and arthralgia for over two thousand years due to its effects of Tong-Luo-Zhi-Tong (dredging collaterals and alleviating pain). Our previous study showed that Chinese medicine Di-Long has significant anti-rheumatoid arthritis (RA) effects. Aim of the studyConsidering Di-Long as a potential source of active compounds with specific anti-RA therapeutic effects, this research was to obtain the anti-RA target-specific active fraction from Di-Long extracts (DL), and to further explore the chemical basis and verify the anti-RA mechanism of this active fraction. Materials and methodsTranscriptomic was applied to obtain the main anti-RA targets of DL on human RA fibroblast-like synoviocytes (FLS) and validated by qPCR. The target-corresponding active fraction was isolated from DL by ethanol precipitation and gel chromatography, and analyzed by nanoliter chromatography-mass spectrometry. Anti-RA effects of this active fraction was investigated by collagen-induced arthritis (CIA) in mice, and anti-RA mechanisms were verified in cocultured model of rat FLS and peripheral blood lymphocytes. ResultsWe confirmed that CXCL10/CXCR3 was the main anti-RA target of DL. The active fraction - A (2182 - 890 Da) was isolated from DL based on its CXCL10 inhibiting effects in RA-FLS. Fraction A contains 195 peptides (192 were newly discovered), 26 of which might be bioactive and were considered to be the chemical basis of its anti-RA effects. Fraction A significantly ameliorated the joint destruction and overall inflammation in CIA mice, and downregulated CXCR3 expression in mice joint. Fraction A inhibited the chemotaxis of Th-cells in rat peripheral blood lymphocytes towards the TNF-α-induced rat FLS through CXCL10/CXCR3 pathway. ConclusionsOur work indicated that active fraction from DL containing small peptides exhibits promising therapeutic effects for RA through inhibiting CXCL10/CXCR3 chemotaxis.

Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.

TNF-α in the serum and synovial fluid of patients with rheumatoid arthritis: correlation with sonographic parameters: a cross-sectional study

BackgroundRheumatoid arthritis (RA) is a chronic, inflammatory joint condition characterized by overproduction of pro-inflammatory cytokines. We aimed to assess TNF-α levels in both serum and synovial fluid in effusive knees in RA patients and find out if synovial fluid levels correlate with ultrasound (US)-detected local knee inflammatory and/or destructive changes in these patients.ResultsThis study included 40 patients (20 with RA, 10 with systemic lupus erythematosus (SLE), and 10 with osteoarthritis (OA)) who had knee effusion (unilateral or bilateral) upon clinical examination. The mean age of RA patients was 48.4 years; most of them were females (80%), with a median (min–max) duration of knee effusion of 2 (1.5–3) months. Serum TNF-α was significantly higher in RA vs. non-RA and in OA cases (p = 0.052, 0.022, respectively), while in the synovial fluid, the difference was not statistically significant (3.73 ± 0.72 vs. 3.48 ± 0.58 U/ml, p = 0.252). Serum TNF-α at a cut point of > 3.24 U/ml can significantly discriminate RA from OA with 65% sensitivity and 90% specificity (AUC = 0.725, P = 0.018). There was no statistically significant correlation between synovial TNF-α and US parameters of the knee, either in RA or non-RA patients.ConclusionsRA, OA, and SLE effusive joints share the presence of local articular joint inflammation, while systemic inflammation is more discriminative for RA patients regarding the level of TNF-α. The lack of correlation of TNF-α with ultrasonographic findings reflects the multifactorial complexity of these autoimmune diseases.

Protective Effects of an Oligo-Fucoidan-Based Formula against Osteoarthritis Development via iNOS and COX-2 Suppression following Monosodium Iodoacetate Injection.

Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and chronic inflammation, accompanied by high oxidative stress. In this study, we utilized the monosodium iodoacetate (MIA)-induced OA model to investigate the efficacy of oligo-fucoidan-based formula (FF) intervention in mitigating OA progression. Through its capacity to alleviate joint bearing function and inflammation, improvements in cartilage integrity following oligo-fucoidan-based formula intervention were observed, highlighting its protective effects against cartilage degeneration and structural damage. Furthermore, the oligo-fucoidan-based formula modulated the p38 signaling pathway, along with downregulating cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, contributing to its beneficial effects. Our study provides valuable insights into targeted interventions for OA management and calls for further clinical investigations to validate these preclinical findings and to explore the translational potential of an oligo-fucoidan-based formula in human OA patients.

Energy landscape analysis and time-series clustering analysis of patient state multistability related to rheumatoid arthritis drug treatment: The KURAMA cohort study.

Rheumatoid arthritis causes joint inflammation due to immune abnormalities, resulting in joint pain and swelling. In recent years, there have been considerable advancements in the treatment of this disease. However, only approximately 60% of patients achieve remission. Patients with multifactorial diseases shift between states from day to day. Patients may remain in a good or poor state with few or no transitions, or they may switch between states frequently. The visualization of time-dependent state transitions, based on the evaluation axis of stable/unstable states, may provide useful information for achieving rheumatoid arthritis treatment goals. Energy landscape analysis can be used to quantitatively determine the stability/instability of each state in terms of energy. Time-series clustering is another method used to classify transitions into different groups to identify potential patterns within a time-series dataset. The objective of this study was to utilize energy landscape analysis and time-series clustering to evaluate multidimensional time-series data in terms of multistability. We profiled each patient's state transitions during treatment using energy landscape analysis and time-series clustering. Energy landscape analysis divided state transitions into two patterns: "good stability leading to remission" and "poor stability leading to treatment dead-end." The number of patients whose disease status improved increased markedly until approximately 6 months after treatment initiation and then plateaued after 1 year. Time-series clustering grouped patients into three clusters: "toward good stability," "toward poor stability," and "unstable." Patients in the "unstable" cluster are considered to have clinical courses that are difficult to predict; therefore, these patients should be treated with more care. Early disease detection and treatment initiation are important. The evaluation of state multistability enables us to understand a patient's current state in the context of overall state transitions related to rheumatoid arthritis drug treatment and to predict future state transitions.

Subclinical joint inflammation in rheumatoid arthritis: comparing thermal and ultrasound imaging at the metacarpophalangeal joint

BackgroundWhile ultrasound and MRI are both superior to clinical examination in the detection of joint inflammation, there is presently a lack of data whether thermography may be similarly useful in the assessment of joint inflammation in patients with RA. Our study aims to evaluate the use of thermography in detecting subclinical joint inflammation at clinically quiescent (non-tender and non-swollen) metacarpophalangeal joints (MCPJs) in patients with rheumatoid arthritis (RA). The outcomes from thermography in our study will be compared with ultrasonography (which is a more established imaging tool used for joint inflammation assessment in RA).MethodsThe minimum (Tmin), average (Tavg) and maximum (Tmax) temperatures at the 10 MCPJs of each patient were summed to obtain the Total Tmin, Total Tavg and Total Tmax, respectively. Ultrasound grey-scale (GS) and power Doppler (PD) joint inflammation (scored semi-quantitatively, 0–3) at the 10 MCPJs were summed up to derive the respective TGS and TPD scores per patient. Pearson’s correlation and simple linear regression were respectively used to assess correlation and characterize relationships between thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TGS, TPD and the number of joint(s) with PD ≥ 1 or GS ≥ 2).ResultsIn this cross-sectional study, 420 clinically non-swollen and non-tender MCPJs from 42 RA patients were examined. All thermographic parameters (Total Tmin, Total Tavg and Total Tmax) correlated significantly (P-values ranging from 0.001 to 0.0012) with TGS score (correlation coefficient ranging from 0.421 to 0.430), TPD score (correlation coefficient ranging from 0.383 to 0.424), and the number of joint(s) with PD ≥ 1 or GS ≥ 2 (correlation coefficient ranging from 0.447 to 0.465). Similarly, simple linear regression demonstrated a statistically significant relationship (P-values ranging from 0.001 to 0.005) between all thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TPD and TGS).ConclusionFor the first time, thermographic temperatures were shown to correlate with ultrasound-detected joint inflammation at clinically quiescent MCPJs. The use of thermography in the detection of subclinical joint inflammation in RA appears promising and warrants further investigation.

Ammodaucus Leucotrichus Seed Extract as a Potential Therapy in Animal Models of Rheumatoid Arthritis Induced by Complete Freund Adjuvant and Chicken Cartilage Collagen.

This study assessed the efficacy of an Ammodaucus leucotrichus seed extract to treat rheumatoid arthritis in rat models of this disease. Rheumatoid arthritis was induced in rats using two methods: immunization with 100 µL of Complete Freund Adjuvant (CFA) and immunization with 100 µL of a 3mg/ml solution of type II collagen (CII) from chicken cartilage. The therapeutic potential of the extract was assessed at different doses (150, 300, and 600mg/kg/day for 21 days in the CII-induced arthritis model and for 14 days in the CFA-induced arthritis model) and compared with methotrexate (MTX; 0.2mg/kg for the same periods), a commonly used drug for rheumatoid arthritis treatment in humans. In both models (CII-induced arthritis and CFA-induced arthritis), walking distance, step length, intra-step distance and footprint area were improved following treatment with the A. leucotrichus seed extract (all concentrations) and MTX compared with untreated animals. Both treatments increased the serum concentration of glutathione and reduced that of complement C3, malondialdehyde and myeloperoxidase. Radiographic data and histological analysis indicated that cartilage destruction was reduced already with the lowest dose of the extract (100mg/kg/dose) in both models. These results show the substantial antiarthritic potential of the A. leucotrichus seed extract, even at the lowest dose, suggesting that it may be a promising alternative therapy for rheumatoid arthritis and joint inflammation. They also emphasize its efficacy at various doses, providing impetus for more research on this extract as a potential therapeutic agent for arthritis.

Effective diagnosis of sacroiliitis in children: evaluating magnetic resonance imaging with the Canadian scoring system.

To reveal the differences by comparing the magnetic resonance imaging (MRI) findings of patients with clinically symptomatic sacroiliitis with those undergoing sacroiliac imaging for other reasons using the Canadian Spondyloarthritis Research Consortium-Sacroiliac Inflammatory Scoring System (SPARCC-SIS). In this retrospective single-center study, sacroiliac MRIs performed between 2017 and 2023 were evaluated from the database. The SPARCC-SIS scoring system is used to evaluate and grade the inflammation of the sacroiliac joints. Mild inflammation is indicated by a score below 24, moderate by a score of 24-48, and severe by a score above 49. Additionally, structural defects of the sacroiliac joint, such as erosion, sclerosis, and ankylosis, were observed. After MRI evaluation, clinically symptomatic (group 1) and non-symptomatic (group 2) patients were divided into two groups. The clinical and laboratory findings of the patients and MRI findings were compared. The patient's age, gender, clinical information from hospital records, acute phase reactants (APRs), and the presence of the Human Leukocyte Antigen (HLA-B27) gene (if applicable) were thoroughly recorded. One hundred thirty-six children who performed sacroiliac MRI for any indication were included in the study. The APRs positivity, presence of HLA-B27, and SPARCC scoring system were significantly higher in 24 patients with clinical sacroiliitis (group 1) than in 112 patients without sacroiliitis (group 2). In our study, the most common MRI findings in children were bone marrow edema, capsulitis, synovitis, and erosion, while chronic structural changes such as sclerosis and ankylosing were rare. In this study, the SPARCC scoring method, which shows the severity of sacroiliac joint inflammation, correlates with the clinical diagnosis of sacroiliitis. In cases with suspected sacroiliitis, except for extraordinary reasons, it can be evaluated with MRI without contrast material and can be graded to guide the clinician in treatment and approach.

Effect of weight loss and exercise on joint pain in patients with osteoarthritis and obesity

Osteoarthritis (OA), the most common joint disease, coexists with obesity in most of the world’s population. According to the forecast of the World Health Organization, the number of patients with these diseases is expected to increase, which represents a serious medical and social problem due to increased disability, the need for surgical treatment, an increase in comorbid diseases, treatment complications and mortality in this group of patients. OA and obesity have common pathogenetic mechanisms, and the development of one disease increases the risk of developing the other, which can become the beginning of a vicious circle. In recent years, obesity is considered not only as a biomechanical factor (excessive load on the joint, destruction of articular cartilage), but also as a cause of metabolic syndrome and systemic inflammatory effects. Inflammatory cytokines, especially IL-1β and TNF-α, drive catabolic pathways and promote the progression of OA. There is compelling evidence that weight loss reduces pain and joint inflammation and improves prognosis in patients with OA. The review presents data on the prevalence of OA and obesity, the role of immune disorders in these diseases, and indicates methods of pharmacological and non-pharmacological treatment of OA. General principles and specific updated recommendations of the European League Against Rheumatism for non-drug treatment of OA of the hip and knee joints are outlined, and recommendations for weight loss through dietary interventions and exercise are formulated.

Deletion of RANKL in regulatory T cells ameliorates bone erosion in arthritis

Abstract Rheumatoid arthritis (RA) is an autoimmune disease that leads to bone erosion mediated through osteoclasts.Osteoclast differentiation is promoted through engagement of RANK by its ligand (RANKL) expressed by multiple lineages. Whereas regulatory T cells (Tregs) typically suppress osteoclastogenesis, Tregs developing in a pro-inflammatory environment can express RANKL and promote osteoclast function (Levescot et al.2021).To test the importance of osteoclastogenic Tregs in vivo, we developed a mouse selectively lacking RANKL expression in Tregs (FoxP3YFP/creRANKLflox/flox, hereafter RANKLΔTreg). Arthritis was induced by administration of K/BxN serum containing arthritogenic IgG antibodies. Joint inflammation and synovial neutrophil infiltration in RANKLΔTreg mice were similar to WT animals. Compared with Tregs from lymph nodes, Tregs from inflamed joints exhibited increased expression of activation markers including CD25,Foxp3,CD44, and CTLA4, without a difference between RANKLΔTreg and WT animals; RANKLΔTreg mice exhibited a trend for higher Treg PD-1 expression. In WT mice, the percentage of Tregs expressing RANKL was elevated in synovial fluid compared to lymph nodes. Correspondingly, microCT showed a significant reduction in bone erosion in RANKLΔTreg compared to WT mice (p=0.003). These findings are consistent with a pathogenic role of RANKL-expressing Treg for RA bone erosion in arthritis; whether RANKL impacts other Treg functions remains to be established.